The objectives are the design, synthesis, and evaluation of novel selective inhibitors of several steroid enzymes of androgen and estrogen biosynthesis. Such compounds are of potential use for regulation of hormonally dependent tumors, e.g., benign prostatic hypertrophy, and some forms of prostatic and mammary carcinoma. They are also of potential use for studies of the endocrine processes regulated by these enzymes, e.g., regulation of epididymal function, sperm storage and maturation in males; reproductive cycle regulation in females; and fetal or neonatal brain masculinization. The major approach entails an attempt to greatly increase the potency and specificity of such enzyme inhibition by the development of "suicide substrates" for the target enzymes. These agents contain latent alkylating groups that are unmasked at the active site of the target enzyme when the enzyme carries out its normal catalytic function. The unmasked alkylating group can then covalently bind to the target enzyme and irreversibly inactivate it. Thus the enzyme catalyzes its own inactivation. Inhibitors of delta-5-3-ketosteroid isomerase, 3-alpha- and 3-beta-hydroxysteroid dehydrogenase will be evaluated with appropriate bacterial enzymes from Pseudomonas testosteroni. Inhibitors of 3-alpha-hydroxysteroid dehydrogenase and delta-4-5-alpha-reductase will also be evaluated in rat epididymal and prostatic homogenates, while inhibitors of aromatase and 3-beta-hydroxysteroid dehydrogenase will be evaluated with human placental microsomes. In vivo effects on male rat androgen-dependent organs and female mouse estrogen-dependent organs will be measured. Effects on rat gonadotropin levels will be determined by radioimmunoassay.